Thornton S, Duwel L E, Boivin G P, Ma Y, Hirsch R
Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Arthritis Rheum. 1999 Jun;42(6):1109-18. doi: 10.1002/1529-0131(199906)42:6<1109::AID-ANR7>3.0.CO;2-7.
To quantitate changes in cytokine and chemokine messenger RNA (mRNA) levels during the development and progression of collagen-induced arthritis (CIA) in mice.
Mice with CIA were scored for arthritis and killed at weekly intervals. Cytokine and chemokine mRNA levels were determined by RNase protection assays of total paw RNA.
Arthritic paws exhibited mRNA levels of interleukin-1beta (IL-1beta), IL-2, macrophage inflammatory protein 2 (MIP-2), IL-6, IL-1 receptor antagonist, RANTES, tumor necrosis factor alpha (TNFalpha), TNFbeta, MIP-1alpha, IL-11, transforming growth factor beta1 (TGFbeta1), TGFbeta2, and TGFbeta3 that were increased above mRNA levels in paws of normal, unimmunized mice and that exhibited distinct temporal patterns of mRNA expression. Clinically uninvolved paws also exhibited an increase in mRNA levels of IL-11, RANTES, TNFalpha, TNFbeta, and MIP-1alpha.
The observed differential temporal cytokine and chemokine mRNA expression patterns suggest that specific cytokines and chemokines have defined roles at various times during the course of autoimmune arthritis. Since most of these cytokines and chemokines are found in human rheumatoid arthritis (RA) synovium and synovial fluids, these findings may have relevance to RA.
定量检测小鼠胶原诱导性关节炎(CIA)发生发展过程中细胞因子和趋化因子信使核糖核酸(mRNA)水平的变化。
对患CIA的小鼠的关节炎症状进行评分,并每周处死一批小鼠。通过对爪部总RNA进行核糖核酸酶保护分析来测定细胞因子和趋化因子的mRNA水平。
患关节炎的爪部白细胞介素-1β(IL-1β)、IL-2、巨噬细胞炎性蛋白2(MIP-2)、IL-6、IL-1受体拮抗剂、调节激活正常T细胞表达和分泌的趋化因子(RANTES)、肿瘤坏死因子α(TNFα)、TNFβ、MIP-1α、IL-11、转化生长因子β1(TGFβ1)、TGFβ2和TGFβ3的mRNA水平高于正常未免疫小鼠爪部的mRNA水平,且呈现出独特的mRNA表达时间模式。临床未受累的爪部IL-11、RANTES、TNFα、TNFβ和MIP-1α的mRNA水平也有所升高。
观察到的细胞因子和趋化因子mRNA表达的不同时间模式表明,特定的细胞因子和趋化因子在自身免疫性关节炎病程的不同阶段发挥着特定作用。由于这些细胞因子和趋化因子大多存在于人类类风湿关节炎(RA)的滑膜和滑液中,这些发现可能与RA有关。